A large body of evidence exists which implicates enterotoxin-producing Escherichia coli as the cause of a high percentage of undiagnosed diarrheas in man. Entertoxigenic E. coli (ETEC) from animal sources have been found to produce an additional virulence factor--species-specific, surface-associated antigens (K88, K99) which confer the ability to colonize the small bowel of certain animals. These K antigens also have mannose-resistant hemagglutinin activity (MR-HA) and appear as piliate structures by electron microscopy. We have been able to detect three serologically distinct protein antigens on ETEC strains isolated from human diarrheal disease. These strains also exhibit MR-HA ability. These adherence pili have been purified from ETEC by a temperature dependent red cell absorption and elution technique. By transmission EM all three types of pili are 5-10 nm x 300 nm in size. Molecular weight determination by SDS-PAGE detected protein subunits of 12,500 and 13,000 daltons in all preparations. Isolated pili have also been shown to bind to human buccal cells. The Gab fragment of anti-pili IgG has been shown to block buccal cell binding by intact bacterial cells. ETEC strains from humans will be compared for their ability to adhere to human buccal epithelial cells and human intestinal cells. The physiologic and genetic control of adherence antigens is being investigated along with a study of their biological properties. Greater understanding of the adherence antigens present on toxigenic i.e. E. coli from humans will then allow the development of specific "blocking" or competing substance(s) designed to interfere with bacterial colonization.